[Diagnosis and screening of sickle cell disease].
Hemoglobin S (HbS), which causes sickle cell disease, is now the most common genetic abnormality observed in France. Sickle cell disease is a generic term covering all the syndromes in which HbS is present. The heterozygous situation, named sickle cell trait, is perfectly well tolerated in contrast to homozygous or compound heterozygous forms, which lead to sickle cell anemia. To prevent complications, diagnosis of HbS has to be done as earlier as possible in the first day of life. This diagnosis is usually done by isoelectric focusing, or cellulose acetate electrophoresis at alkaline pH, but more and more frequently by cation exchange HPLC. It should always to be confirmed by a specific test for HbS, such as the solubility test or an electrophoresis on agar gel. In sickle cell anemia, it is important to evaluate the other factors that may modify the presentation (mostly HbF level and associated alpha-thalassemia). In a heterozygous subject presenting with pathological manifestations, more sophisticated biochemical tests or molecular biology investigations may be necessary to determine the cause of the disease.


Structural Study of Nano-Sized Gahnite (ZnAl2O4): From the Average to the Local Scale.
Spinel gahnite (ZnAl2O4) has been obtained through a hydrothermal synthesis method with a grain size of about 2 nm. The sample was calcined for a few hours at two different temperatures (800 and 900 °C) in order to obtain larger grain sizes to be analyzed by means of powder diffraction with the Rietveld method, and by means of total scattering with the Pair Distribution Function (PDF) method. The idea is to compare the average to the local structure, as a function of increasing grain size. The total scattering data were collected at the European Synchrotron Radiation Facility (ESRF), Grenoble. The samples have been also characterised by means of high resolution Transmission Electron Microscopy (TEM), showing an increasing grain size up to about 9 nm. The average structure presented variations in the inversion degree and an increase in grain size. TEM observations demonstrated that the small crystals are well crystallised: the high resolution images neatly showed the atomic planes, even in the smallest particles. However, the average structure did not properly fit the PDF data in the local region, owing to a slightly different coordination among the octahedra. A new structural model is proposed for the local region of the PDF, that helped our understanding of the differences between a real nanostructured sample and that of a microcrystalline one. The oxygen disorder, due to the inversion grade of the spinel, is demonstrates to be at the basis of the local deviation. No signals of interstitial Zn atoms were detected.


Annual report of the Australian National Poliovirus Reference Laboratory, 2004.
The Australian National Poliovirus Reference Laboratory at the Victorian Infectious Diseases Reference Laboratory is the World Health Organization designated laboratory for the isolation and testing of poliovirus from clinical specimens within Australia, the Pacific Island countries and Brunei Darussalam. Surveillance for acute flaccid paralysis (AFP) within Australia, the main clinical manifestation of poliomyelitis, is also coordinated at the Victorian Infectious Diseases Reference Laboratory in conjunction with the Australian Paediatric Surveillance Unit. The annual non-polio acute flaccid paralysis rate after classification of cases by the Polio Expert Committee was 1.0 per 100,000 population, reaching the expected World Health Organization annual target for a non-polio endemic country. During 2004, 64 specimens from 30 AFP cases were referred to the National Polio Reference Laboratory. A mixture of poliovirus types 1 and 2 was isolated from an infant with AFP from New South Wales. Both isolates tested as Sabin-like and the case was subsequently classified as infant botulism by the Polio Expert Committee. The laboratory isolated adenoviruses from seven AFP cases. A coxsackievirus B5 and an echovirus 18 were identified from a further two AFP cases. During 2004, 1,266 cases of poliomyelitis due to wild poliovirus were reported world-wide. Many of these resulted from wild poliovirus importations, which continued in 2005, including to Indonesia. This highlights the need for maintaining high poliovirus vaccination coverage to prevent the transmission of poliovirus and high quality AFPand laboratory surveillance for the detection of poliomyelitis due to an imported wild poliovirus.


Thyroid-stimulating antibody assay using a human thyrotropin receptor transfected cell line: relationship to clinical features of graves' disease.
To evaluate a Chinese hamster ovary cell line transfected with the human thyrotropin (thyroid-stimulating hormone or TSH) receptor (CHO-TSHR) for its use in routine clinical testing and compare it with the currently used Fisher rat thyroid cell line (FRTL-5) relative to the cyclic adenosine monophosphate (cAMP) responses to thyroid-stimulating antibodies (TSAb). We analyzed 112 serum samples prospectively. TSAb were measured concurrently by both CHO-TSHR cells and FRTL-5 cells. In addition, thyrotropin-binding inhibitory immunoglobulin (TBII) was measured by a radioreceptor assay. Among the study subjects, 51 had active Graves' disease, 40 had other thyroid disease, and 21 had no thyroid disease. Of 51 patients with Graves' disease, 38 (74%) had positive results in both cell assays, 4 (8%) had negative results in both assays, and 9 (18%) had positive responses with CHO-TSHR cells but negative results with FRTL-5 cells. No patient had negative findings with CHO-TSHR cells and positive results by FRTL-5 cells. All 61 patients in the other two groups had negative results by both assays (diagnostic specificity = 100%). The diagnostic sensitivity and accuracy of TSAb activity by the two cell lines (CHO-TSHR versus FRTL-5) were 92.2% versus 74.5% and 96.4% versus 88.4%, respectively. A significant correlation was noted between the TSAb activities in active Graves' sera by the two assays (r = 0.58; P<0.0001); however, values by the CHO-TSHR method were significantly higher (P<0.003). TSAb activities determined with both cell lines were positively correlated with the 24-hour thyroidal 131 I uptake (r = 0.62 and P<0.0005 in CHO-TSHR cells; r = 0.41 and P<0.05 in FRTL-5 cells). The difference in TSAb activity between patients with ophthalmopathy and those without ophthalmopathy was statistically significant with both FRTL-5 (P<0.01) and CHO-TSHR (P = 0.05) assays. The correlation between the severity of eye disease and TSAb activities was significant only with the FRTL-5 assay (P = 0.009) but not with the CHO-TSHR assay (P = 0.16). TSAb activity showed a significant positive correlation with serum thyroxine, triiodothyronine, and TBII by both cell assays. Neither cell line showed a significant correlation between TSAb activity and antimicrosomal antibody titer. The CHO-TSHR cell line is superior to the standard FRTL-5 cell line in the cAMP bioassay for TSAb with reference to diagnostic sensitivity and accuracy, correlation with disease activity, simplicity, and cost.


Nutritional antioxidants and the modulation of inflammation: theory and practice.
Highly potent substances are produced by the immune system. These substances include cytokines and oxidant molecules, such as hydrogen peroxide, free radicals, and hypochlorous acid. The purpose of immune cell products is to destroy invading organisms and damaged tissue, bringing about recovery. However, oxidants and cytokines can damage healthy tissue. Excessive or inappropriate production of these substances is associated with mortality and morbidity after infection and trauma, and in inflammatory diseases. Oxidants enhance interleukin-1, interleukin-8, and tumor necrosis factor production in response to inflammatory stimuli by activating the nuclear transcription factor, NF kappa B. Sophisticated antioxidant defenses directly and indirectly protect the host against the damaging influence of cytokines and oxidants. Indirect protection is afforded by antioxidants, which reduce activation of NF kappa B, thereby preventing up-regulation of cytokine production by oxidants. Cytokines increase both oxidant production and antioxidant defenses, thus minimizing damage to the host. While antioxidant defenses interact when a component is compromised, the nature and extent of the defenses are influenced by dietary intake of sulfur amino acids, for glutathione synthesis, and vitamins E and C. In animal studies, in vivo and in vitro responses to inflammatory stimuli are influenced by dietary intake of copper, zinc, selenium, N-acetylcysteine, cysteine, methionine, taurine, and vitamin E. Information from animal studies has yet to be fully translated into a clinical context. However, N-acetylcysteine, vitamin E, and a cocktail of antioxidant nutrients have reduced inflammatory symptoms in inflammatory joint disease, acute and chronic pancreatitis, and adult respiratory distress syndrome. Impaired antioxidant defenses may contribute to disease progression after infection with human immunodeficiency virus. Powerful arguments have been advanced for treatment with antioxidants to slow progression of acquired immunodeficiency syndrome.


Dosimetrical verification of calculated total and gamma absorbed dose distributions DT, respectively DG, for fast neutron therapy.
The physical part of treatment planning for neutron therapy is highly important but quite more complicated than for photons and electrons due to the necessity of separation of total and gamma absorbed dose distributions (DT and DG). Therefore, dosimetrical verifications of dose distributions of complex treatment plans are very rare, and the experimental difficulties are enormous. A method using TLD-300 (CaF2: Tm) detectors is described with the ability to provide from each detector's readings both DT and DG using the different LET dependence of the main glow-curve peaks. The principle of an on-line computer program is given for an automatic mathematical glow-curve analysis which is necessary to achieve the accuracy of about +/- 5% (DT) and +/- 10% (DG) in single fixed fields. Dosimetrically relevant features of the TLD-300 method are discussed. Examples of dosimetrical verifications of calculated dose distributions (DT and DG) for a treatment with one single fixed field, with two wedge filter fields and with a rotational field with d(14)+Be neutrons are shown. Deviations exceeding significantly the uncertainties above are found only in the case of the wedge filter treatment for the absolute (quite less for the relative) values of the DG dose distribution. Probable reasons are mostly the reduced contribution of scattered radiation for phantom sizes, which laterally scarcely exceed the useful beam, and slight neutron energy spectrum changes by the wedge filter.


Norepinephrine Regulates Keratinocyte Proliferation to Promote the Growth of Hair Follicles.
Psychological factors and stress can cause hair loss. The sympathetic-adrenal-medullary (SAM) axis has been reported to regulate the growth of hair follicles (HF). The sympathetic nerve is a component of the SAM axis, but it has not been sufficiently or convincingly linked to hair growth. In this study, we demonstrate that chemical sympathectomy via administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to mice inhibited HF growth, but treatment with the β-adrenoceptor antagonist propranolol (PR) had no effect. HF length and skin thickness were greater in PR-treated and control mice than in 6-OHDA-treated mice, as evidenced by hematoxylin and eosin staining. Furthermore, we found that the reduced HF growth in sympathectomized animals was accompanied by a decreased keratinocyte proliferation. Moreover, the neurotransmitter norepinephrine (NE) was found to efficiently promote HF growth in an organotypic skin culture model. Together, these findings suggest that sympathetic nerves regulate keratinocyte behaviors to promote hair growth, providing novel insights into stress-related, chemotherapy-, and radiotherapy-induced alopecia.


Laboratory techniques for rabies diagnosis in animals at QSMI.
The Queen Saovabha Memorial Institute (QSMI), Thai Red Cross Society was founded in 1922 to carry out the production of the nervous tissue vaccines, post-exposure prophylaxis (PEP) treatment, research, and laboratory diagnosis. The diagnostic laboratory had replaced the Seller's staining with direct fluorescent test (DFA) as standard technique in 1987 and the mouse inoculation technique (MIT) had been employed as the confirmatory test to ensure the result of the diagnosis. Other techniques conducted at our facility such as tissue culture infection and polymerase chain reaction techniques are less practical although the sensitivity is competitive with DFA but mainly for research references.


Genotypic discrepancies arising from imputation.
The ideal genetic analysis of family data would include whole genome sequence on all family members. A strategy of combining sequence data from a subset of key individuals with inexpensive, genome-wide association study (GWAS) chip genotypes on all individuals to infer sequence level genotypes throughout the families has been suggested as a highly accurate alternative. This strategy was followed by the Genetic Analysis Workshop 18 data providers. We examined the quality of the imputation to identify potential consequences of this strategy by comparing discrepancies between GWAS genotype calls and imputed calls for the same variants. Overall, the inference and imputation process worked very well. However, we find that discrepancies occurred at an increased rate when imputation was used to infer missing data in sequenced individuals. Although this may be an artifact of this particular instantiation of these analytic methods, there may be general genetic or algorithmic reasons to avoid trying to fill in missing sequence data. This is especially true given the risk of false positives and reduction in power for family-based transmission tests when founders are incorrectly imputed as heterozygotes. Finally, we note a higher rate of discrepancies when unsequenced individuals are inferred using sequenced individuals from other pedigrees drawn from the same admixed population.


In-vitro release and oral bioactivity of insulin in diabetic rats using nanocapsules dispersed in biocompatible microemulsion.
This study evaluated the potential of poly(iso-butyl cyanoacrylate) (PBCA) nanocapsules dispersed in a biocompatible microemulsion to facilitate the absorption of insulin following intragastric administration to diabetic rats. Insulin-loaded PBCA nanocapsules were prepared in-situ in a biocompatible water-in-oil microemulsion by interfacial polymerisation. The microemulsion consisted of a mixture of medium-chain mono-, di- and tri-glycerides as the oil component, polysorbate 80 and sorbitan mono-oleate as surfactants and an aqueous solution of insulin. Resulting nanocapsules were approximately 200 nm in diameter and demonstrated a high efficiency of insulin entrapment (> 80%). In-vitro release studies showed that PBCA nanocapsules could suppress insulin release in acidic media and that release at near neutral conditions could be manipulated by varying the amount of monomer used for polymerisation. Subcutaneous administration of insulin-loaded nanocapsules to diabetic rats demonstrated that the bioactivity of insulin was largely retained following this method of preparing peptide-loaded nanocapsules and that the pharmacodynamic response was dependent on the amount of monomer used for polymerisation. The intragastric administration of insulin-loaded nanocapsules dispersed in the biocompatible microemulsion resulted in a significantly greater reduction in blood glucose levels of diabetic rats than an aqueous insulin solution or insulin formulated in the same microemulsion. This study demonstrates that the formulation of peptides within PBCA nanocapsules that are administered dispersed in a microemulsion can facilitate the oral absorption of encapsulated peptide. Such a system can be prepared in-situ by the interfacial polymerisation of a water-in-oil biocompatible microemulsion.


Targeted therapy in Ewing sarcoma.
Despite marked improvement in the prognosis of patients with nonmetastatic Ewing sarcoma (ES), the outcome for patients with recurrent or metastatic disease remains poor. Insight into key biologic processes in ES could provide new therapeutic targets. The particular biologic feature of ES, the fusion of the EWS gene with a member of the ETS family of genes, is present in >95% of cases. The EWS-ETS chimeric protein leads to aberrant transcription that promotes tumor initiation and propagation via prosurvival and antiapoptotic pathways. Recent research has identified cooperating mutations important for ES tumorigenesis. This paper provides a summary of the latest research in ES and discusses potential novel targets for therapy.


Increased gene expression variability hinders the formation of regional mechanical conflicts leading to reduced organ shape robustness.
To relate gene networks and organ shape, one needs to address two wicked problems: i) Gene expression is often variable locally, and shape is reproducible globally; ii) gene expression can have cascading effects on tissue mechanics, with possibly counterintuitive consequences for the final organ shape. Here, we address such wicked problems, taking advantage of simpler plant organ development where shape only emerges from cell division and elongation. We confirm that mutation in VERNALIZATION INDEPENDENCE 3 (VIP3), a subunit of the conserved polymerase-associated factor 1 complex (Paf1C), increases gene expression variability in Arabidopsis. Then, we focused on the Arabidopsis sepal, which exhibits a reproducible shape and stereotypical regional growth patterns. In vip3 sepals, we measured higher growth heterogeneity between adjacent cells. This even culminated in the presence of negatively growing cells in specific growth conditions. Interestingly, such increased local noise interfered with the stereotypical regional pattern of growth. We previously showed that regional differential growth at the wild-type sepal tip triggers a mechanical conflict, to which cells resist by reinforcing their walls, leading to growth arrest. In vip3, the disturbed regional growth pattern delayed organ growth arrest and increased final organ shape variability. Altogether, we propose that gene expression variability is managed by Paf1C to ensure organ robustness by building up mechanical conflicts at the regional scale, instead of the local scale.


Trichotillomania, stereotypic movement disorder, and related disorders.
Trichotillomania is currently classified as an impulse control disorder not otherwise classified, whereas body-focused behaviors other than hair-pulling may be diagnosed as stereotypic movement disorder. A number of disorders characterized by repetitive, body-focused behaviors (eg, skin-picking) are prevalent and disabling and may have phenomenological and psychobiological overlap. Such disorders deserve greater recognition in the official nosology, and there would seem to be clinical utility in classifying them in the same diagnostic category.


Factors influencing the diagnostic accuracy of the rapid influenza antigen detection test (RIADT): a cross-sectional study.
To evaluate the diagnostic accuracy of the rapid influenza antigen detection test (RIADT) and determine which symptoms are relevant to results. Single-centre, cross-sectional study. Primary care centre, Tokyo, Japan. 82 consecutive outpatients presenting with upper respiratory symptoms and fever ≥37°C at any time from symptom onset, between December 2010 and April 2011. Results of history and physical examination including age, sex, temperature, time of test from symptom onset, vaccination record and current symptoms (sore throat, arthralgia and/or myalgia, headache, chills, cough and/or throat phlegm, nasal discharge) were recorded. The RIADT and a fully automated respiratory virus nucleic acid test (Verigene Respiratory Virus Plus; VRV), the latter being the gold standard, were performed. Patients were divided into four groups: false negative (FN), RIADT- and VRV+; true positive (TP), RIADT+ and VRV+; true negative (TN), RIADT- and VRV-; and false positive, RIADT+ and VRV-. Groups were compared regarding age, sex, temperature, time of test from symptom onset, vaccination record and symptoms. RIADT sensitivity, specificity, positive predictive value and negative predictive value were 72.9% (95% CI 61.5% to 84.2%), 91.3% (79.7% to 102.8%), 95.6% (89.5% to 101.6%) and 56.8% (40.8% to 72.7%), respectively. Time from symptom onset to test was shorter for the FN group than the TP group (p=0.009). No significant differences were detected for the other factors assessed. Results revealed higher temperatures for FN than TN patients (p=0.043), and more FN than TN patients had chills (p=0.058). The RIADT sensitivity was low, due to early administration of the test. In the epidemic season, the RIADT should not be used for suspected influenza until 12 h after symptom onset. A positive RIADT firmly supports the influenza diagnosis; a negative result does not confirm its absence. High fever and chills might indicate influenza, but additional tests are sometimes necessary.


Metal-free oxidative C(sp(3))-H bond functionalization of alkanes and alkylation-initiated radical 1,2-aryl migration in α,α-diaryl allylic alcohols.
An oxidative C(sp(3))-H bond functionalization of alkanes and alkylation-initiated radical 1,2-aryl migration in α,α-diaryl allylic alcohols using di-tert-butyl peroxide (DTBP) as the oxidant was established, which tolerates a wide range of simple alkane substrates and α,α-diaryl allylic alcohols for direct preparation of α-aryl-β-alkylated carbonyl ketones.


Pup exposure elicits hippocampal cell proliferation in the prairie vole.
The onset of parental behavior has profound and enduring effects on behavior and neurobiology across a variety of species. In some cases, mere exposure to a foster neonate (and a subsequent parental response) can have similar effects. In the present experiment, we exposed adult male and female prairie voles (Microtus ochrogaster) to two foster pups for 20 min and quantified cell proliferation in the dentate gyrus of the hippocampus (DG), medial amygdala (MeA) and cortical amygdala (CorA). Prairie voles are highly social rodents that typically display biparental care and spontaneous parental care when exposed to foster pups. Comparisons were made between the animals that responded parentally or non-parentally towards the pups, as well as control conditions. Cell proliferation was assessed using injections of 5-bromo-2'-deoxyuridine (BrdU) and immunocytochemical localization of this marker. The phenotype of the cells was determined using double label immunofluoresence for BrdU and TuJ1 (a neuronal marker). An increase in cell proliferation in the DG was seen in animals exposed to pups. However, animals that responded non-parentally had a greater number of BrdU labeled cells in the DG compared to those that responded parentally. The majority of BrdU labeled cells co-expressed TuJ1 across all groups. These results demonstrate that exposure to a foster pup and the behavioral reaction to it (parental or non-parental) are associated with site-specific changes in cell proliferation.


Disentangle First, Then Distill: A Unified Framework for Missing Modality Imputation and Alzheimer's Disease Diagnosis.
Multi-modality medical data provide complementary information, and hence have been widely explored for computer-aided AD diagnosis. However, the research is hindered by the unavoidable missing-data problem, i.e., one data modality was not acquired on some subjects due to various reasons. Although the missing data can be imputed using generative models, the imputation process may introduce unrealistic information to the classification process, leading to poor performance. In this paper, we propose the Disentangle First, Then Distill (DFTD) framework for AD diagnosis using incomplete multi-modality medical images. First, we design a region-aware disentanglement module to disentangle each image into inter-modality relevant representation and intra-modality specific representation with emphasis on disease-related regions. To progressively integrate multi-modality knowledge, we then construct an imputation-induced distillation module, in which a lateral inter-modality transition unit is created to impute representation of the missing modality. The proposed DFTD framework has been evaluated against six existing methods on an ADNI dataset with 1248 subjects. The results show that our method has superior performance in both AD-CN classification and MCI-to-AD prediction tasks, substantially over-performing all competing methods.


Azlocillin pharmacokinetics in patients with cystic fibrosis.
The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified times after the last dose of the course of azlocillin therapy and then assayed for azlocillin content. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for serum half-life (1.74 h), disposition constant (0.41 h-1), total body clearance (123 ml/kg per h), and renal clearance (58 ml/kg per h) were determined. All patients exhibited improvement with respect to clinical and laboratory parameters and displayed no adverse reactions. The pharmacokinetic analysis offers further evidence of the dose-dependent nature of azlocillin elimination, but elimination did not appear to be altered in cystic fibrosis patients.


Double-blind, randomized, controlled, crossover trial of pregabalin for neurogenic claudication.
To test the effects of pregabalin on the induction of neurogenic claudication. This study was a randomized, double-blind, active placebo-controlled, 2-period, crossover trial. Twenty-nine subjects were randomized to receive pregabalin followed by active placebo (i.e., diphenhydramine) or active placebo followed by pregabalin. Each treatment period lasted 10 days, including a 2-step titration. Periods were separated by a 10-day washout period, including a 3-day taper phase after the first period. The primary outcome variable was the time to first moderate pain symptom (Numeric Rating Scale score ≥4) during a 15-minute treadmill test (Tfirst). Secondary outcome measures included pain intensity at rest, pain intensity at the end of the treadmill test, distance walked, and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire, modified Brief Pain Inventory-Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire. No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom (difference in median Tfirst = -1.08 [95% confidence interval -2.25 to 0.08], p = 0.61). In addition, none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo. Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis. This study provides Class I evidence that for patients with neurogenic claudication, compared with diphenhydramine, pregabalin does not increase the time to moderate pain during a treadmill test.


Cell-cycle analysis in 20 minutes.
Mithramycin added to mammalian cells fixed in aqueous ethanol is bound to DNA and fluoresces in direct proportion to the cellular DNA content. Quantitative fluorescence measurement by means of a high-speed flow system instrument provides a rapid method for cell-cycle analysis and for the first time permits continuous monitoring of cell-cycle kinetics during ongoing experiments.


High Strain Rate Superplasticity in Al-Zn-Mg-Based Alloy: Microstructural Design, Deformation Behavior, and Modeling.
Increasing the strain rate at superplastic forming is a challenging technical and economic task of aluminum forming manufacturing. New aluminum sheets exhibiting high strain rate superplasticity at strain rates above 0.01 s-1 are required. This study describes the microstructure and the superplasticity properties of a new high-strength Al-Zn-Mg-based alloy processed by a simple thermomechanical treatment including hot and cold rolling. The new alloy contains Ni to form Al3Ni coarse particles and minor additions of Zr (0.19 wt.%) and Sc (0.06 wt.%) to form nanoprecipitates of the L12-Al3 (Sc,Zr) phase. The design of chemical and phase compositions of the alloy provides superplasticity with an elongation of 600-800% in a strain rate range of 0.01 to 0.6/s and residual cavitation less than 2%. A mean elongation-to-failure of 400% is observed at an extremely high constant strain rate of 1 s-1. The strain-induced evolution of the grain and dislocation structures as well as the L12 precipitates at superplastic deformation is studied. The dynamic recrystallization at superplastic deformation is confirmed. The superplastic flow behavior of the proposed alloy is modeled via a mathematical Arrhenius-type constitutive model and an artificial neural network model. Both models exhibit good predictability at low and high strain rates of superplastic deformation.


Differential neuropsychiatric symptom responses to tacrine in Alzheimer's disease: relationship to dementia severity.
Neuropsychiatric symptom responses to tacrine were investigated in an open-label study of Alzheimer's outpatients. Forty subjects were stratified into three groups (Mild, Moderate, and Severe) based on Mini-Mental State Examination scores. A significant reduction in total Neuropsychiatric Inventory score across all subjects was principally attributable to changes in the Moderate group. Apathy and disinhibition symptoms were significantly reduced overall. Whereas other symptoms showed differential responses in Mild and Severe subjects, all symptoms improved in Moderate subjects. These findings suggest that disease severity may significantly influence neuropsychiatric symptom responses to tacrine. Putative mechanisms underlying the observed pattern of responses are explored.


Effects of laser trabeculoplasty on the human aqueous humor dynamics: a fluorophotometric study.
Thirteen eyes, seven with primary open-angle glaucoma and six with capsular glaucoma, were treated with laser trabeculoplasty (a fluorophotometric examination was performed about one week prior to it). The intraocular pressure was reduced below 20 mm Hg in eight eyes, and the second fluorophotometric examination could be carried out in six successfully treated eyes about three months later. In the six successfully treated eyes, the pre-laser trabeculoplasty examination showed the following results: IOP: 22 +/- 2 mm Hg; the cornea-aqueous transfer coefficient for fluorescein: 0.32 +/- 0.10 hour-1; and the aqueous flow rate: 1.31 +/- 0.53 microliter min-1. The post-laser trabeculoplasty examination gave the following results: IOP: 15 +/- 2 mm Hg; the cornea-aqueous transfer coefficient: 0.29 +/- 0.08 hour-1; and the aqueous flow rate: 1.23 +/- 0.41 microliter min-1. No significant difference was found in the aqueous flow rate or the cornea-aqueous transfer coefficient before and after.


Resemblances of twins and their parents in pattern A behavior.
A twin study was conducted to determine the relative contribution of genetic and environmental factors to the development of Pattern A behavior. Thirty-five sets of college-aged MZ twins and 21 sets of DZ twins completed the lenkins Activity Survey for Health Prediction. This self-administering questionnaire yields scales measuring Pattern A behavior and its related traits of Speed and Impatience, Job Involvement, and Hard-driving Competitiveness. Results showed a modest genetic component for the Hard-driving Competitive aspect of Pattern A. Data were also presented regarding resemblances between the twins and their parents on Pattern A.


[Achievement and Philosophy of Studies on SPECT Reconstruction Algorithms].
The purpose of this article is to introduce achievement and philosophy on studies of SPECT reconstruction algorithms which Dr. Eiichi Tanaka dedicated himself to carrying out. The method that Dr. Tanaka suggested first (in 1974) was to reconstruct analytically a section image from the projection data convoluted the correction functions. The correction functions were optimized to yield a maximum 'signal-to-noise ratio'. In 1983 and 1984, two image reconstruction algorithms, WBP and RPC were suggested assuming a uniform attenuation in the object. Dr. Tanaka understood intuitively that these methods had few noise and distortions in reconstructed images. WBP was an approximate solution, but three type analytically methods were reported by Tretiak O, et al., Bellini S, et al., and Inoyue T, et al. In 1995, Metz CE, et al. and Kudo H, et al. succeeded independently each other in finishing a general theory of the analytic absorption Radon Conversion by using parameter "n". The relations among the above three analytically methods and WBP were explained, beautifully. The important thing in the study is a flexible idea such as catching a problem as the issue of black box or reverse and the result to be concise and elegant.


Ureter as the Content in a Large Inguino Scrotal Hernia: A Diagnostic Dilemma for Unprepared Surgeons.
We present a case of a 60-year-old gentleman, who was referred for an inguinal hernia repair. A previous CT scan had reported a right pelvic kidney and the presence of the right ureter in the hernial sac. He had no urinary symptoms and there was no biochemical evidence of compromised renal function. A renogram showed partial obstruction with an equally split function. The findings were discussed in a urological multi-disciplinary team (MDT) meeting. A ureteric stent was advised to assist in the identification of the ureter during the surgery. The patient had intraoperative stenting of the right ureter, followed by successful repair of the hernia. Six weeks later, the stent was removed, and the patient continues to remain well. Follow-up blood results showed normal renal functions.


Household polluting cooking fuels and adverse birth outcomes: An updated systematic review and meta-analysis.
The current study aimed to clarify the association between household polluting cooking fuels and adverse birth outcomes using previously published articles. In this systematic review and meta-analysis, a systematic literature search in PubMed, Embase, Web of Science, and Scopus databases were undertaken for relevant studies that had been published from inception to 16 January 2023. We calculated the overall odds ratio (OR) and 95% confidence interval (CI) for adverse birth outcomes [low birth weight (LBW), small for gestational age (SGA), stillbirth, and preterm birth (PTB)] associated with polluting cooking fuels (biomass, coal, and kerosene). Subgroup analysis and meta-regression were also conducted. We included 16 cross-sectional, five case-control, and 11 cohort studies in the review. Polluting cooking fuels were found to be associated with LBW (OR: 1.37, 95% CI: 1.24, 1.52), SGA (OR: 1.48, 95% CI: 1.13, 1.94), stillbirth (OR: 1.38, 95% CI: 1.23, 1.55), and PTB (OR: 1.27, 95% CI: 1.19, 1.36). The results of most of the subgroup analyses were consistent with the main results. In the meta-regression of LBW, study design (cohort study: P < 0.01; cross-sectional study: P < 0.01) and sample size (≥ 1000: P < 0.01) were the covariates associated with heterogeneity. Cooking fuel types (mixed fuel: P < 0.05) were the potentially heterogeneous source in the SGA analysis. The use of household polluting cooking fuels could be associated with LBW, SGA, stillbirth, and PTB. The limited literature, observational study design, exposure and outcome assessment, and residual confounding suggest that further strong epidemiological evidence with improved and standardized data was required to assess health risks from particular fuels and technologies utilized.


Clinical features and prognosis of retroperitoneal hemangiosarcoma in dogs with surgical resection with or without adjuvant doxorubicin.
Retroperitoneal hemangiosarcoma (RPHSA) is a rare tumor in dogs with a poorly understood prognosis after surgery. The objectives of this study were to investigate the clinical features and prognosis of canine RPHSA that had undergone surgical resection. In this single-center, retrospective cohort study, we reviewed the medical records of dogs that had undergone surgical resection for retroperitoneal tumors and received a histopathologic diagnosis of HSA between 2005 and 2021. The median progression-free survival (PFS) and overall survival (OS) were 77.5 days and 168 days, respectively. In the present study, canine RPHSA had an aggressive biological behavior similar to visceral HSA. Further studies in larger canine populations are needed to evaluate the efficacy of adjuvant chemotherapy.


Photoelectron velocity-map imaging spectroscopic and theoretical study on the reactivity of the gold atom toward CH3SH, CH3OH, and H2O.
Photoelectron velocity-map imaging spectroscopy has been used to study the reaction of the anionic gold atom with the HR (R = SCH3, OCH3, OH) molecules. The solvated [Au···HR](-) and inserted [HAuR](-) products have been experimentally observed for R = SCH3, whereas only solvated [Au⋯HR](-) products were found for R = OCH3 and OH. This significant difference in the photoelectron spectra suggests the different reactivity of the Au(-) toward the CH3SH, CH3OH, and H2O molecules. Second order Møller-Plesset perturbation theory and coupled-cluster single double triple excitation calculations have been performed to aid the structural assignment of the spectra and to explore the reaction mechanism. Activation energies for the isomerizations of the solvated structures to the inserted ones in the Au(-)∕Au + HR reactions (R = OCH3 and OH) are predicted to be much higher than those for the Au(-)∕Au + CH3SH reactions, supporting the experimental observation. Theoretical calculations provide the evidence that the intriguing [HAuSCH3](-) product may be formed by the attachment of the electron onto the neutral HAuSCH3 species or the isomerization from the anionic [Au···HSCH3](-) one. These findings should be helpful for understanding the feature that the thiols are able to form the staple motifs, whereas CH3OH and H2O are not.


Seasonal changes in the digesta-adherent rumen bacterial communities of dairy cattle grazing pasture.
The complex microbiota that resides within the rumen is responsible for the break-down of plant fibre. The bacteria that attach to ingested plant matter within the rumen are thought to be responsible for initial fibre degradation. Most studies examining the ecology of this important microbiome only offer a 'snapshot' in time. We monitored the diversity of rumen bacteria in four New Zealand dairy cows, grazing a rye-grass and clover pasture over five consecutive seasons, using high throughput pyrosequencing of bacterial 16S rRNA genes. We chose to focus on the digesta-adherent bacterial community to learn more about the stability of this community over time. 16S rRNA gene sequencing showed a high level of bacterial diversity, totalling 1539 operational taxonomic units (OTUs, grouped at 96% sequence similarity) across all samples, and ranging from 653 to 926 OTUs per individual sample. The nutritive composition of the pasture changed with the seasons as did the production phase of the animals. Sequence analysis showed that, overall, the bacterial communities were broadly similar between the individual animals. The adherent bacterial community was strongly dominated by members of Firmicutes (82.1%), followed by Bacteroidetes (11.8%). This community differed between the seasons, returning to close to that observed in the same season one year later. These seasonal differences were only small, but were statistically significant (p < 0.001), and were probably due to the seasonal differences in the diet. These results demonstrate a general invariability of the ruminal bacterial community structure in these grazing dairy cattle.


Unique Characteristics of New Bone Formation Induced by Lateral Lumbar Interbody Fusion Procedure.
Despite the absence of bone grafting in the area outside the cage, lateral bridging callus outside cages (LBC) formation is often observed here following extreme lateral interbody fusion (XLIF) conversely to conventional methods of transforaminal lumbar interbody fusion and posterior lumbar interbody fusion. The LBC, which may increase stabilization and decrease nonunion rate in treated segments, has rarely been described. This study aimed to identify the incidence and associated factors of LBC following XLIF. We enrolled 136 consecutive patients [56 males, 80 females; mean age 69.6 (42-85) years] who underwent lumbar fusion surgery using XLIF, including L4/5 level with posterior fixation at a single institution between February 2013 and February 2018. One year postoperatively, the treated L4/5 segments were divided into the LBC formation and non-formation groups. Potential influential factors, such as age, sex, body mass index, bone density, height of cages, cage material (titanium or polyetheretherketone [PEEK]), presence or absence of diffuse idiopathic skeletal hyperostosis (DISH), and radiological parameters, were evaluated. Multivariate logistic regression analysis was performed for factors significantly different from the univariate analysis. The incidence of LBC formation was 58.8%. Multivariate logistic regression analysis showed that the length of osteophytes [+1 mm; odds ratio, 1.29; 95% confidence interval, 1.17-1.45; p<0.0001] was significant LBC formation predictive factors. Receiver operating characteristic curve analysis demonstrated that the cut-off value for osteophyte length was 14 mm, the sensitivity was 58.8%, the specificity was 84.4%, and the area under the ROC curve for this model was 0.79. The incidence of LBC formation was 58.8% in L4/5 levels one year after the XLIF procedure. We demonstrated that the length of the osteophyte was significantly associated with LBC formation.


Surgical robotics: impact of motion scaling on task performance.
Robotic systems have been shown to enhance surgical dexterity, and the advantage has been hypothesized to result from the removal of tremor and addition of motion scaling. But these purported gains over traditional laparoscopic instrumentation have not been quantified. This study was designed to compare the surgical accuracy between conventional laparoscopic instruments and a robotic surgical system and evaluate the importance of tremor filtration (TF) and motion scaling (MS) in these robotic systems. Fifteen participants with no previous surgical experience were enrolled. To simulate microsurgical techniques, a 29-gauge needle was used to puncture the center of 6 microscopic archery targets (circle diameters 0.5, 1.5, and 2.5 mm). The robotic system was configured to three different degrees of MS and compared with the unassisted laparoscopic platforms in accuracy. Accuracy with robotic assistance with TF alone (1:1 MS) was not significantly different from unassisted laparoscopic control. Both moderate (2.5:1) and fine (7:1) MS significantly improved accuracy over traditional laparoscopic control (p < 0.001 for both). Robotic assistance with MS equalized the performance of both hands (p = 0.03) in precision, and manual laparoscopy demonstrated no statistical difference in handedness (p = 0.80). Motion scaling, rather than tremor filtration, plays the major role in the enhanced accuracy seen in robotic surgical systems. Robotic assistance with MS significantly improved accuracy above laparoscopic instruments alone and robotic assistance with tremor filtration alone. MS also creates ambidexterity in an otherwise unidextrous population, optimizing the surgeon's ability to undertake tasks requiring microsurgical accuracy.


Vitamin E and Its Molecular Effects in Experimental Models of Neurodegenerative Diseases.
With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be better elucidated, which justifies the publication of reviews that explore the mechanisms related to the development of these diseases. Studies show that vitamin E supplementation can protect neurons from the damage caused by oxidative stress, with a positive impact on the prevention and progression of neurodegenerative diseases. Thus, this review aims to summarize the scientific evidence of the effects of vitamin E supplementation on neuroprotection and on neurodegeneration markers in experimental models. A search for studies published between 2000 and 2023 was carried out in the PubMed, Web of Science, Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in experimental models of neurodegeneration were investigated. A total of 5669 potentially eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253 were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after fully reviewing the manuscripts, leaving 19 publications to be included in this review. Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E supplementation significantly improved memory, cognition, learning, motor function, and brain markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation reduced beta-amyloid (Aβ) deposition and toxicity in experimental models of Alzheimer's disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to indicate the potential use of vitamin E in preventing and delaying the progress of degenerative lesions in the central nervous system.


Using lidar to assess the development of structural diversity in forests undergoing passive rewilding in temperate Northern Europe.
Forested areas are increasing across Europe, driven by both reforestation programs and farmland abandonment. While tree planting remains the standard reforestation strategy, there is increased interest in spontaneous regeneration as a cost-effective method with equal or potentially greater benefits. Furthermore, expanding areas of already established forests are left for passive rewilding to promote biodiversity conservation. Effective and objective methods are needed for monitoring and analyzing the development of forest structure under these management scenarios, with airborne laser scanning (lidar: light detection and ranging) being a promising methodology. Here, we assess the structural characteristics and development of unmanaged forests and 28- to 78-year old spontaneously regenerated forests on former agricultural land, relative to managed forests of similar age in Denmark, using 25 lidar-derived metrics in 10- and 30-m grid cells. We analyzed the lidar-derived cell values in a principal component analysis (PCA) and interpreted the axes ecologically, in conjunction with pairwise tests of median and variance of PCA-values for each forest. Spontaneously regenerated forest in general had increased structural heterogeneity compared to planted and managed forests. Furthermore, structural heterogeneity kept increasing in spontaneously regenerated forest across the maximal 78-year timespan investigated. Natural disturbances showed strong impacts on vegetation structure, leading to both structural homogeneity and heterogeneity. The results illustrate the utility of passive rewilding for generating structurally heterogeneous forested nature areas, and the utility of lidar surveys for monitoring and interpreting structural development of such forests.


Causes of inadequate protein-energy status in thalassemic children.
Height-for-age, weight-for-age, triceps skinfold thickness (TST), mid upper arm circumference (MUAC), and mid upper arm muscle circumference (UAMC) were determined in 47 thalassemic children, ages ranging from 4- 5 years. Their mean (± SEM) height-for-age, weight-for age, TST, MUAC, and UAMC were 90.51± 0.98, 79.91± 2.33, 88.01± 1.26, 83.02± 1.37 and 80.09± 1.59% of standard values. Based on height-forage of less than 95% of standard values and weight-for-age, TST, MUAC, and UAMC of less than 90% of standard values, the prevalences of protein-energy malnutrition (PEM) in these thalassemic children were 72.3,74.5,53.7,75.6 and 82.9%, respectively. The causes of their inadequate protein-energy status were due to: (a) chronic hypoxia evidenced by the significantly positive correlations between haemoglobin levels and height-for-age (r=0.65, P<0.001), weight-for-age (r=0.58, P<0.001), MUAC (r=0.67, P<0.001) and UAMC (r=0.63, P<0.001); (b) zinc deficiency evidenced by significantly positive correlations between plasma zinc levels and height-for-age (r=0.26, P<0.05), MUAC (r=0.41, P<0.005), and UAMC (r=0.41, P<0.005) and significantly negative correlation between urinary zinc levels and UAMC (r=0.34, P<0.02); and (c) low energy intake, ie 65% of the mean recommended energy intake.


In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenograft model of gastric cancer using two-photon laser scanning microscopy.
We previously visualized in vivo responses to chemotherapy in a colorectal liver metastatic xenograft model using in vivo real-time and time-series intravital two-photon laser scanning microscopy (TPLSM). In this study, we established the method for evaluating the response of peritoneal xenografts to chemotherapy of metastatic gastric cancer using intravital TPLSM. Red fluorescent protein-expressing gastric cancer cells (NUGC4) were inoculated into the peritoneal cavity of green fluorescent protein nude mice. Laparotomy revealed that 2 weeks after inoculation, macroscopic peritoneal metastatic nodules were formed. The first intravital TPLSM session revealed that they were composed of red tumor cell clusters and green surrounding stroma. Paclitaxel was administered intraperitoneally after the first TPLSM three times a week for 7 days in the treatment group. At the second laparotomy, there were significantly fewer and smaller nodules in the treated mice than in the controls. The second intravital TPLSM session showed tumor cell fragmentation, swelling, and nuclear condensation in the metastatic nodules--a response to chemotherapy. There were multinuclear tumor cells in the paclitaxel-treated living mice. Our method may become a powerful tool for evaluating the efficacy of novel anti-gastric cancer drugs in a preclinical murine model with minimum interindividual variation.


Short- and mid-term results of plica excision in patients with mediopatellar plica and associated cartilage degeneration.
This study aimed to evaluate the short- and mid-term results of plica excision in patients with mediopatellar plica and associated cartilage degeneration. Seventy-six surgically treated patients with mediopatellar plica and associated cartilage degeneration at medial femoral condyle (MFC) and/or medial pole of patella were included. Patients were evaluated at baseline, at 6 weeks and 6 months after the operation for their clinical outcomes and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The frequency of all signs and symptoms, including all pain parameters, and WOMAC scores were significantly improved compared to baseline, at 6 weeks and 6 months after the operation (P < 0.017). Based on mean WOMAC scores, results of most patients were rated as excellent both at 6 weeks (88%) and at 6 months (94%). Surgical excision of mediopatellar plica associated with cartilage degeneration appears to result in substantial clinical improvement, thus it represents an effective treatment modality.


The effect of monochromatic photostimulation on growth and development of broiler birds.
The only light source for chickens in environmentally controlled houses is an artificial one. Thus, source, spectra, intensity and regimen of light supplementation became major factors in modern meat type bird management. Light spectra affect growth in meat type birds both in ovo and post hatch. Broilers photostimulated in ovo with green light gained significantly more weight than birds incubated under dark conditions. Furthermore, we defined the cellular and molecular events associated with the effect of in ovo green photostimulation on muscle growth. We found that in ovo photostimulation have a stimulatory effect on the proliferation and differentiation of satellite cells and a promoting effect on the uniformity of the muscle fibers in the early post-hatch period. How does in ovo photostimulation affect intracellular events, such as proliferation and differentiation of muscle cells, leading to post-hatch muscle growth? It is possible that the monochromatic green light penetrates the eggshell and has a direct effect on the embryo's muscle. We were unable to detect any proliferative effect of monochromatic green light on cultured myoblasts derived from standard (un-illuminated) E17 embryos and 3-day-old chicks. A more likely explanation is that green light indirectly affects myoblast proliferation by activating the endocrine system; the latter receives photic cues from the retinal or extra-retinal photoreceptors. We gathered some evidence to support these findings; we have shown a higher expression of growth hormone (GH) receptor mRNA in satellite cells derived from green light illuminated chicks. In addition, plasma GH levels and IGF-I levels in muscle tissue, were higher in the green group relative to the dark one in early post-hatch. Another possible explanation for this phenomenon could be that growth factor secretion is activated in response to green light photostimulation. Both retinal and extra-retinal photoreceptors are active during embryogenesis and can be first detected at E14. Combinations of in ovo and post-hatch green light photostimulation to broilers and turkeys did not cause synergetic effect on growth. In a recent study, we found that in ovo green light photostimulation suppresses the green and red opsin receptors gene expression in the last three days before hatching, while red light enhances their expression. Furthermore, we found that the down-regulation of the green and red opsins in response to incubation under monochromatic green lighting lasted up to 9days post hatch, suggesting a possible epigenetic effect.


Double geminal C-H activation and reversible alpha-elimination in 2-aminopyridine iridium(III) complexes: the role of hydrides and solvent in flattening the free energy surface.
[H2Ir(OCMe2)2L2]BF4 (1) (L = PPh3), a preferred catalyst for tritiation of pharmaceuticals, reacts with model substrate 2-(dimethylamino)pyridine (py-NMe2; py = 2-pyridyl) to give chelate carbene [H2Ir(py-N(Me)CH=)L2]BF4 (2a) via cyclometalation, H2 loss, and reversible alpha-elimination. Agostic intermediate [H2Ir(py-N(Me)CH2-H)L2]BF4) (4a), seen by NMR, is predicted (DFT(B3PW91) computations) to give C-H oxidative addition to form the alkyl intermediate [(H)(eta2-H2)Ir(py-N(Me)CH2-)L2]BF4. Loss of H2 leads to the fully characterized alkyl [HIr(OCMe2)(py-N(Me)CH2-)L2]BF4 (3a(Me2CO)), which loses acetone to give alkylidene hydride 2a by rapid reversible alpha-elimination. 2a rapidly reacts with excess H2 in d6-acetone to generate [H2Ir(OC(CD3)2)2L2]BF4 (1-d12), 3a((CD3)2CO), and py-NMe2 in a 1:1:1 ratio, showing reversibility and accounting for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH2)4 gives the fully characterized carbene 2c. A cis-L(2) carbene intermediate, cis-2c, observed by NMR, reacts with CO via retro alpha-elimination to give the alkyl 3cCO, while the trans isomer, 2c, does not react; retro alpha-elimination thus requires the Ir-H bond to be orthogonal to the carbene plane. Consistent with experiment, computational studies show a particularly flat PE surface with activation of the agostic C-H bond giving a less stable H2 complex, then formation of a kinetic carbene complex with cis-L, only seen experimentally for py-N(CH2)4. Hydrides at key positions, together with gain or loss of solvent and H2, flatten the PE (DeltaG) surfaces to allow fast catalysis.


Production of antibody against ochratoxin A.
Antibody against ochratoxin A was obtained after repeated injection of different protein-ochratoxin A conjugates to rabbits. Among many protein-ochratoxin conjugates tested, bovine serum albumin-ochratoxin A was found to be the best antigen. The antibody is specific for ochratoxins A, C, and T, but is not specific for ochratoxins B, alpha, and other coumarin derivatives. The sensitivity for ochratoxin A detection using a binding assay is in the range of 0.5 to 10 ng/0.5-ml sample. Detailed methods for the preparation of protein-ochratoxin conjugates, preparation of immune serum, and methods for antibody titers are described.


Skin peptides: biological activity and therapeutic opportunities.
The skin provides an effective barrier to the loss of body fluids and environmental assault. In addition to the physical barrier provided by the stratum corneum, the skin also contains a chemical barrier consisting of antimicrobial peptides (AMPs), which control microbial growth on the surface. These AMPs also have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing cell proliferation, wound healing, cytokine/chemokine production and chemotaxis. This review describes the range of peptides found in the skin, both constitutive and those induced in response to injury. The role these peptides play in normal skin function and in various skin conditions is described. A better understanding of their role in normal and skin disease may offer new strategies in skin disease, dermatology and as cosmeceuticals.


The dynamic relationship between health expenditure and economic growth: is the health-led growth hypothesis valid for Turkey?
The well-known health-led growth hypothesis claims a positive correlation between health expenditure and economic growth. The aim of this paper is to empirically investigate the health-led growth hypothesis for the Turkish economy. The bound test approach, autoregressive-distributed lag approach (ARDL) and Kalman filter modeling are employed for the 1975-2013 period to examine the co-integration relationship between economic growth and health expenditure. The ARDL model is employed in order to investigate the long-term and short-term static relationship between health expenditure and economic growth. The results show that a 1 % increase in per-capita health expenditure will lead to a 0.434 % increase in per-capita gross domestic product. These findings are also supported by the Kalman filter model's results. Our findings show that the health-led growth hypothesis is supported for Turkey.


Crash data quality for road safety research: Current state and future directions.
Crash databases are one of the primary data sources for road safety research. Therefore, their quality is fundamental for the accuracy of crash analyses and, consequently the design of effective countermeasures. Although crash data often suffer from correctness and completeness issues, these are rarely discussed or addressed in crash analyses. Crash reports aim to answer the five "W" questions (i.e. When?, Where?, What?, Who? and Why?) of each crash by including a range of attributes. This paper reviews current literature on the state of crash data quality for each of these questions separately. The most serious data quality issues appear to be: inaccuracies in crash location and time, difficulties in data linkage (e.g. with traffic data) due to inconsistencies in databases, severity misclassification, inaccuracies and incompleteness of involved users' demographics and inaccurate identification of crash contributory factors. It is shown that the extent and the severity of data quality issues are not equal between attributes and the level of impact in road safety analyses is not yet entirely known. This paper highlights areas that require further research and provides some suggestions for the development of intelligent crash reporting systems.


Surface area and volume changes during maturation of reticulocytes in the circulation of the baboon.
Changes in the surface area and volume of reticulocytes were measured in vivo during late stage maturation. Baboons were treated with erythropoietin to produce mild reticulocytosis. Reticulocyte-rich cohorts of cells were obtained from whole blood by density gradient centrifugation. The cohorts were labeled with biotin, reinfused into the animal, and recovered from whole blood samples by panning on avidin supports. Changes in the surface area, volume, and membrane deformability were measured using micropipettes during the 2 to 6 weeks subsequent to reinfusion. For the entire cohort, the membrane area decreased by 10% to 15% and the cell volume decreased by approximately 8.5%, mostly within 24 hours after reinfusion. Estimates of the cellular dimensions of the reticulocyte subpopulation within this cohort indicated larger reductions in the mean cell area (12% to 30%) and mean cell volume (approximately 15%) of the reticulocytes themselves. Two weeks after reinfusion, the distribution of cell size for the cohort was indistinguishable from that of whole blood. There was evidence of slightly elevated membrane shear rigidity in some reticulocytes before reinfusion, but this slight increase disappeared within 24 hours after reinfusion. These are the first direct measurements of changes in the membrane physical properties of an identifiable cohort of reticulocytes as they mature in vivo.


Transient engraftment of T cell-depleted allogeneic bone marrow in mice improves survival rate following lethal irradiation.
C3H/HeJ mice were exposed to 8 or 9 Gy total body irradiation prior to transplantation of 1-15 x 10(6) H-2 incompatible T cell-depleted bone marrow cells from C57BL/6 donors. Survival was greatly enhanced compared to irradiated controls, even at the lowest cell doses. Analysis of spleen cells 1-7 weeks post-transplant revealed that recipients of the lowest doses of T cell-depleted bone marrow had only transient engraftment of donor type cells, and that long-term recovery was autologous. This transient engraftment had a marked beneficial effect both on reconstitution of hematopoiesis and on survival.


A Comparison of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Insulin Injection in Children with Type I Diabetes in Kuwait: Glycemic Control, Insulin Requirement, and BMI.
Continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) are two methods currently used to manage type I diabetes mellitus (T1DM). Here we compare our experiences with CSII and MDI in a large cohort of pediatric patients in Kuwait. Data on 326 patients with T1DM who were started on CSII between 2007 and 2012 were retrospectively compared with those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM duration, glycemic control, insulin requirement, and body mass index (BMI). Data were collected at baseline and every three months and included glycated hemoglobin (HbA1c), insulin dose, and adverse events (severe hypoglycemia, diabetic ketoacidosis, and skin problems). The main reason for switching to CSII was to achieve better glycemic control (37%), followed by reducing hypoglycemia, and improving the quality of life (13.3% each). Although HbA1c decrease was most significant in the first year, it continued to be significantly lower in the CSII group compared to the MDI throughout the study period. Total daily insulin requirements were significantly lower in the CSII group. BMI increased in both groups, but the difference was significant only at the end of the fifth year. There was no significant change in the rate of diabetic ketoacidosis in either group. The CSII patients had more severe hypoglycemic episodes at baseline; however, it significantly decreased throughout the study period. Only five patients discontinued CSII therapy and two of these restarted within three months. CSII is a safe intensive insulin therapy in youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and lower daily insulin requirements.


Review of the ultrastructure of the nematode body cuticle and its phylogenetic interpretation.
The phylogenetic interpretation of the nematode cuticle ultrastructure is reviewed within the framework of recent DNA-sequence data. In particular, the structure of the median and basal zones is discussed. Several structural elements of the cuticle seem to have arisen independently several times within the Nematoda and thus are highly homoplasious (e.g. the cortical or basal radial striae, spiral fibre layers and a fluid matrix with struts). Moreover, identifying the homology of the nematode cuticle ultrastructures is often very difficult at deep taxonomic levels. Hence, the cuticle appears to be unreliable regarding resolution of deep-level relationships in the Nematoda. However, at less inclusive taxonomic levels (e.g. families, genera, ...) the cuticle seems to be a more reliable phylogenetic marker.


Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level.
Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.05 and 1.2 mg/kg body weight/day, were administered intraperitoneally for 5 days to mice. Both treatments impaired the structure of the hepatic mitochondria, although oxygen consumption rate and expression of the respiratory complex decreased only at the higher dose. The hepatic levels of malondialdehyde (MDA), a naturally occurring product of lipid peroxidation, increased, while the expression of glutathione peroxidase 3 (GPx3) decreased, after BPA treatment. The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) also increased. In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential. In conclusion, doses of BPA below the NOAEL induce mitochondrial dysfunction in the liver, and this is associated with an increase in oxidative stress and inflammation.


Structural studies of the O-chains of the lipopolysaccharides produced by strains of Actinobacillus (Haemophilus) pleuropneumoniae serotype 5.
The water-phase lipopolysaccharides isolated by phenol-water extraction from the cells of four strains of Actinobacillus pleuropneumoniae serotype 5 (K17, L20, B78-3760, and 81-750) were shown on structural analysis to have O-chain components with the same basic polysaccharide structure of a linear unbranched homopolymer of 1,6-linked beta-D-galactopyranosyl residues, although the linear length of the O-chain varied among different strains. While those of strains B78-3760 and 81-750 were partially O-acetylated, the O-chains of strains K17 and L20 were unsubstituted.


[Preparation and identification of polyclonal antibody of Streptococcus salivarius 57.I urease].
To prepare and identify polyclonal antibody of Streptococcus salivarius 57.I urease. The biggest structural subunit of Streptococcus salivarius 57.I urease, UreC, was obtained by gene clone, IPTG-induced expression, and purification through affinity chromatography. Anti-sera and polyclonal antibody were raised by immunizing rabbits with purified UreC. Western blot was utilized to detect the specific combination of polyclonal antibody with UreC. Purified UreC protein was prepared and used as antigen to immunize rabbits. Polyclonal antibody was obtained, and Western blot displayed a specific band of the polyclonal antibody with UreC about 62 kD as anticipated. Polyclonal antibody against Streptococcus salivarius 57.I urease is obtained, which provides an important tool to explore the function of urease and its relationship with dental caries.


Social support and positive health practices in early adolescents: a test of mediating variables.
This study examines the relationship between social support and positive health practices in early adolescents and tests two variables, loneliness and hopefulness, that theoretically mediate this relationship. The final sample of the study consisted of 134 adolescents, ages 12 to 14, who responded to instruments measuring social support, loneliness, hopefulness, and positive health practices in classroom settings. Correlational analysis supported the five hypothesized relationships. A series of regression analyses indicated that loneliness and hopefulness each were weak mediators of the relationship between social support and positive health practices. Implications for nursing practice are addressed.


Induced pluripotent stem cells in modeling and cell-based therapy of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by neuromuscular degeneration and the progressive loss of upper and lower motor neurons (MNs), causing weakness and paralysis. However, the underlying mechanisms of this disease are still unknown and there is no cure, or even treatment to stop or reverse its pathology. Consequently, most ALS patients die within 3 - 5 years after disease onset. While considerable progress has been made in studying animal models of ALS, they lack clinical suitability due to genetic differences. However, the recent development of induced pluripotent stem cells (iPSCs) has made it possible to study human disease-specific neuronal and glial cells to identify disease mechanisms and develop phenotypic screens for drug discovery. iPSCs provide researchers with a model of naturally occurring pathology under the human genetic background and MNs differentiated from human iPSCs bearing ALS-associated mutations offer a powerful model to study disease pathology. This paper reviews recent methods of differentiating iPSCs into neuronal cells and suggests further applications of these iPSCs-derived cells for ALS disease modeling, drug screening, and possible cell-based therapy.


Efficient variant of algorithm FastICA for independent component analysis attaining the Cramér-Rao lower bound.
FastICA is one of the most popular algorithms for independent component analysis (ICA), demixing a set of statistically independent sources that have been mixed linearly. A key question is how accurate the method is for finite data samples. We propose an improved version of the FastICA algorithm which is asymptotically efficient, i.e., its accuracy given by the residual error variance attains the Cramér-Rao lower bound (CRB). The error is thus as small as possible. This result is rigorously proven under the assumption that the probability distribution of the independent signal components belongs to the class of generalized Gaussian (GG) distributions with parameter alpha, denoted GG(alpha) for alpha > 2. We name the algorithm efficient FastICA (EFICA). Computational complexity of a Matlab implementation of the algorithm is shown to be only slightly (about three times) higher than that of the standard symmetric FastICA. Simulations corroborate these claims and show superior performance of the algorithm compared with algorithm JADE of Cardoso and Souloumiac and nonparametric ICA of Boscolo et al. on separating sources with distribution GG (alpha) with arbitrary alpha, as well as on sources with bimodal distribution, and a good performance in separating linearly mixed speech signals.


Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases.
Ecto-nucleotidase activity is involved in the infection process of Leishmania and various other parasites that enables modulation of host immune responses to promote disease progression. One of the enzymes responsible for this activity is the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase). The enzyme hydrolyzes nucleotides tri- and/or di-phosphate into monophosphate products, which are subsequently hydrolyzed into adenosine. These nucleotides can serve as purinergic signaling molecules involved in diverse cellular processes that govern immune responses. Given the importance of the extracellular metabolism of these nucleotides during intracellular pathogen infections, this study evaluates the role of ecto-nucleotidase activity during Leishmania infantum (L. infantum) infection in human macrophages. E-NTPDase protein expression and activity was evaluated in L. infantum during purine starvation, adenosine-enriched medium, or in the presence of an inhibitor of ecto-nucleotidases. Results show that E-NTPDase is expressed in L. infantum parasites, including on the cell membrane. Furthermore, functional activity of the enzyme was modulated according to the availability of adenosine in the medium. Purine starvation increased the hydrolytic capacity of nucleotides leading to higher infectivity, while growth in adenosine-enriched medium led to lower infectivity. Moreover, inhibiting E-NTPDase function decreased L. infantum infection in macrophages, suggesting the enzyme may serve as a ligand. Taken together, the ability of L. infantum to hydrolyze nucleotides is directly associated with increased infectivity in macrophages.


Early and later onset type 2 diabetes in uninsured patients: clinical and behavioral differences.
The national burden of type 2 diabetes mellitus (T2DM) is increasing rapidly. This study investigated a) clinical differences between early onset and later onset T2DM; and b) if specific risk factors were associated with age at diagnosis or clinical outcomes among uninsured adults in a large urban setting. We compared 417 adults diagnosed under age 30 with 968 adults diagnosed ages 50-58 on clinical and social measures using standard parametric tests. Early onset patients had higher hemoglobin A1c, were more likely to smoke and to be depressed, and had more emergency department visits. Insulin monotherapy was more common in early onset patients (32% vs. 11%). Complications were already present in 11% of early onset patients and 29% of later onset patients within one year of diagnosis. Early onset patients had more acute beta-cell failure and coped less well with their diabetes. It is crucial to expand specialized diabetes resources for young, medically indigent patients.


COVID-19 Impact on Stroke Admissions during France's First Epidemic Peak: An Exhaustive, Nationwide, Observational Study.
The coronavirus disease 2019 (COVID-19) pandemic continues to have great impacts on the care of non-COVID-19 patients. This was especially true during the first epidemic peak in France, which coincided with the national lockdown. The aim of this study was to identify whether a decrease in stroke admissions occurred in spring 2020, by analyzing the evolution of all stroke admissions in France from January 2019 to June 2020. We conducted a nationwide cohort study using the French national database of hospital admissions (Information Systems Medicalization Program) to extract exhaustive data on all hospitalizations in France with at least one stroke diagnosis between January 1, 2019, and June 30, 2020. The primary endpoint was the difference in the slope gradients of stroke hospitalizations between pre-epidemic, epidemic peak, and post-epidemic peak phases. Modeling was carried out using Bayesian techniques. Stroke hospitalizations dropped from March 10, 2020 (slope gradient: -11.70), and began to rise again from March 22 (slope gradient: 2.090) to May 7. In total, there were 23,873 stroke admissions during the period March-April 2020, compared to 29,263 at the same period in 2019, representing a decrease of 18.42%. The percentage change was -15.63%, -25.19%, -18.62% for ischemic strokes, transient ischemic attacks, and hemorrhagic strokes, respectively. Stroke hospitalizations in France experienced a decline during the first lockdown period, which cannot be explained by a sudden change in stroke incidence. This decline is therefore likely to be a direct, or indirect, result of the COVID-19 pandemic.


[Psychiatric and clinico-psychologic epidemiology: critique of methods and systematization approach].
The development of typical epidemiological questions is discussed. Possible definitions und fields of applications for simple status-diagnostics as well as for epidemiological longitudinal research are presented. Examples for the application of complex mathematical models like LOGIT- or LISREL-analysis are presented. Insufficient methodological systematisation and problems in comparing studies of different origin (i.e. for metaanalysis) are identified as problems for the future development of epidemiology. A classification system of epidemiological methods is presented that includes content aspects as well as methodological aspects on four levels. These are: the demand of the study (descriptive vs. inferential), the time dimension (status diagnostics vs. longitudinal research), the content level of operationalisation (micro- vs. macrolevel) and the level of explanation (correlative vs. causal). Examples show that this system can be used for classification of existing studies as well as for the conceptualisation and optimization of planned studies.


Stability of perpendicular magnetohydrodynamic shocks in materials with ideal and nonideal equations of state.
Magnetized target fusion approach to inertial confinement fusion involves the formation of strong shocks that travel along a magnetized plasma. Shocks, which play a dominant role in thermalizing the upstream kinetic energy generated in the implosion stage, are seldom free from perturbations, and they wrinkle in response to upstream or downstream disturbances. In Z-pinch experiments, significant plasma instability mitigation was observed with pre-embedded axial magnetic fields. To isolate effects, in this work we theoretically study the impact of perpendicular magnetic fields on the planar shock dynamics for different equations of state. For fast magnetosonic shocks in ideal gases, it was found that the magnetic field amplifies the intensity of the perturbations when γ>2 or it weakens them when γ<2. Weak shocks have been found to be stable regardless of the magnetic plasma intensity and gas compressibility; however, for sufficiently strong shocks the magnetic fields can promote a neutral stability/SAE at the shock if the adiabatic index is higher than 1+sqrt[2]. Results have been validated with numerical simulations performed with the FLASH code.


Full-space metasurface holograms in the visible range.
Conventional metasurface holography is usually implemented in either transmission space or reflection space. Herein, we show a dielectric metasurface that can simultaneously project two independent holographic images in the transmission and reflection spaces, respectively, merely with a single-layer design approach. Specifically, two types of dielectric nanobricks in a nanostructured metasurface are employed to act as half-wave plates for geometric phase modulation. One type of nanobrick is designed to reflect most of incident circularly-polarized light into reflection space, enabled with magnetic resonance, while another type of nanobrick transmits it into transmission space, without resonance involved. By controlling the orientation angles and randomly interleaving the two types of nanobricks to form a metasurface, a full-space metasurface hologram can be established. We experimentally demonstrate this trans-reflective meta-holography by encoding the geometric phase information of two independent images into a single metasurface, and all observed holographic images agree well with our predictions. Our research expands the field-of-view of metasurface holography from half- to full-space, which can find its markets in optical sensing, image displays, optical storages and many other potential applications.


The Revised American Occupational Therapy Association Fieldwork Performance Evaluations: Evaluation of Internal Structure, Response Processes, and Precision-Part 2.
There is an evidence-based need to assess the validity and reliability/precision of the revised American Occupational Therapy Association's Fieldwork Performance Evaluation (FWPE) items for the occupational therapy student (OTS) and the occupational therapy assistant student (OTAS). To evaluate evidence of validity in relation to response processes, internal structure, and precision of the FWPEs. Cross-sectional study design. OTS and OTAS fieldwork practice settings, United States. Two hundred sixty-seven fieldwork educators participated in total, providing 228 OTS evaluations and 39 OTAS evaluations. A Rasch model was used to evaluate aspects of validity and precision. The rating scales provided evidence of the tools' overall validity. Thirty-two of 37 items on the FWPE for the OTS, and 27 of 31 items on the FWPE for the OTAS demonstrated acceptable fit, but the evidence of unidimensionality in the subscales and in the total scales was not fully supported. The total/reduced FWPE scales were able to separate students into at least four distinct groups of fieldwork performance. The relationships between the current and revised FWPEs indicate that the new scales measure different but related constructs of student fieldwork performance, compared with the current version. The findings support that the revised FWPEs for the OTS and OTAS demonstrate preliminary evidence of internal structure, response processes, and precision, supporting evidence-based practice in fieldwork evaluations. What This Article Adds: This article highlights evidence demonstrating the validity and precision of the revised American Occupational Therapy Association's Fieldwork Performance Evaluation items and supports academic and fieldwork settings for occupational therapy students and occupational therapy assistant students.


Use of an Intraoperative Limb Positioner for Adjustable Distraction in Acetabulum Fractures with Femoral Head Protrusion: A Case Report.
Anatomic reduction of acetabular fractures with femoral head protrusion requires lateralization of the medialized femoral head to facilitate reduction and definitive fixation. In this case of a 71-year-old man with an associated both column acetabular fracture with femoral head medialization after a fall from a 10 foot ladder, we present the successful use of a novel reduction technique involving a modified arthroscopic limb positioner to provide adjustable distraction and counteract the deforming force in this injury pattern. A limb positioner can provide appropriate on-table traction in pelvis and acetabular surgery to neutralize deforming forces and facilitate reduction and fixation.


Sacrococcygeal teratomas: a review of 68 cases.
Sixty-eight cases of sacrococcygeal teratoma were reviewed and graded according to the quantity of immature tissue present. Seventy-five percent were benign (grade 0), 11.8% immature (Grades 1-3), and 13.2% malignant. Although the immature component in most tumors was neuroepithelial, in two cases it was exclusively renal. There were no instances of local recurrence or metastasis of immature elements. The malignant lesions were all endodermal sinus tumor, stained positively for alpha-fetoprotein and were uniformly fatal, with an average duration of survival of 8.9 months. Early adequate treatment of sacrococcygeal teratomas results in a favorable prognosis. This experience is different from that reported for immature ovarian teratomas. Immature metanephric tissue in sacrococcygeal teratomas should be interpreted the same way as immature neuroepithelial elements. Immature sacrococcygeal teratomas should be separated from tumors containing malignant elements because of their vastly different prognoses.


Elevated Concentrations of SERPINE2/Protease Nexin-1 and Secretory Leukocyte Protease Inhibitor in the Serum of Patients with Papillary Thyroid Cancer.
Introduction. SERPINE2 and secretory leukocyte protease inhibitor (SLPI) are proteins with anticoagulant properties which could promote solid tumor growth. However, their role in the pathogenesis of thyroid cancer has not been determined. Materials and Methods. The aim of this study was to assess serum SERPINE2 and SLPI concentrations in a group of 36 patients with papillary thyroid cancer (PTC) and a group of 19 subjects with multinodular nontoxic goiter (MNG). The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum SERPINE2 and SLPI concentrations were measured using specific ELISA methods. Results. Significantly higher concentrations of SERPINE2 and SLPI were found in patients with PTC as compared with MNG and controls. Positive correlation was found between SERPINE2 and SLPI concentrations in PTC patients. The levels of SERPINE2 and SLPI did not differ significantly between MNG and healthy controls. Conclusions. Our results indicate that SERPINE2 and SLPI play a significant role in the development of papillary thyroid cancer and imply that the evaluation of serum concentrations of both anticoagulant molecules may be considered as additional marker for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors.


[Melatonin therapeutic use in psychiatry: a 39 year bibliographic study].
The therapeutic uses of melatonin in psychiatry are reviewed. Data source and search strategy: a 39 year period search covering a 39 year period (1966-2004) was carried out using Medline data base. The search strategy consisted in the combination of the key words ((mental disorders or psychiatry)) and ((melatonin and therapeutic use)). Two restrictive criteria were applied: a) selection of studies carried out in humans, and b) only randomized controlled trials were admitted 56 articles were found. Twelve were excluded because they were not directly related to the study aim. Melatonin was used in 44 articles related to different clinical conditions. It was used because of its hypnotic and/or resynchronizing actions in 93.2 % of the articles, while in 4.5 % of the articles melatonin was used due to its antioxidant properties. The main use of melatonin as a therapeutic agent in psychiatry is in sleep disorders and its use in other psychiatric is minor.


Hormonal regulation of female nuptial coloration in a fish.
Physiological color change in camouflage and mating is widespread among fishes, but little is known about the regulation of such temporal changes in nuptial coloration and particularly concerning female coloration. To better understand regulation of nuptial coloration we investigated physiological color change in female two-spotted gobies (Gobiusculus flavescens). Females of this species develop an orange belly that acts as an ornament. The orange color is caused by the color of the gonads combined with the chromathophore based pigmentation and transparency of the skin. Often during courtship and female-female competition, a rapid increase in orange coloration, in combination with lighter sides and back that increases skin and body transparency, gives the belly an intense 'glowing' appearance. To understand how this increased orange coloration can be regulated we analysed chromatic and transparency effects of neurohumoral agents on abdominal skin biopsies in vitro. We found prolactin and alpha-melanocyte stimulating hormone (MSH) to increase orange coloration of the skin. By contrast, melatonin and noradrenaline increased skin transparency, but had a negative effect on orange coloration. However, mixtures of melatonin and MSH, or melatonin and prolactin, increased both orange coloration and transparency. This effect mimics the chromatic 'glow' effect that commonly takes place during courtship and intra sexual aggression. Notably, not only epidermal chromatophores but also internal chromatophores lining the peritoneum responded to hormone treatments. There were no chromatic effects of the sex steroids 17beta-estradiol, testosterone or 11-ketotestosterone. We hypothesize that similar modulation of nuptial coloration by multiple hormones may be widespread in nature.


Fib-4 Predicts Early Hematological Adverse Events Induced by Interferon-Based Triple Therapy in Chronic Hepatitis C Virus Patients.
Interferon-alpha (IFN-α)-based therapy is associated with several hematological adverse events in hepatitis C virus (HCV)-infected patients with advanced fibrosis. We performed this study to evaluate the association between Fibrosis-4 (Fib-4) index and hematological adverse events in patients with chronic HCV infection, undergoing IFN-α-based triple therapy. We included 120 HCV-infected patients, receiving triple therapy: weekly PegIFN-α, daily ribavirin (1,000-1,200 mg), and daily sofosbuvir (400 mg) for 12 weeks. We compared Fib-4 scores for patients who developed hematological adverse events at weeks 4 (w4) and w12 of treatment and w12 post-treatment versus those who did not. Treatment with the aforementioned triple regimen was associated with a sustained virological response (SVR)-12 rate of 93.9%. We found no significant associations (P > 0.05) between SVR12 rate and the degree of fibrosis or the risk of hematological adverse events. The Fib-4 score could predict patients who developed hematological adverse events (anemia, leukopenia, and neutropenia) in the first month of treatment, but not in later stages. A Fib-4 cutoff value of 3.59 had high specificity for anemia, leukopenia, and neutropenia (85.1%, 87.2%, and 88.2%, respectively), but had low sensitivity for detecting the 3 events. In conclusion, the Fib-4 score may predict early hematological adverse effects in HCV-infected patients on IFN-based triple therapy.


Topiramate use in obese patients with binge eating disorder: an open study.
To assess topiramate's efficacy and tolerability in a group of obese binge eaters with no neuropsychiatric comorbidity. We consecutively selected 8 obese patients with binge eating disorder (BED) and no medical or psychiatric comorbidity from individuals seeking treatment for obesity. Treatment with topiramate at 150 mg daily was administered over a 16-week period. To assess outcome, we employed the days with binge episodes per week (DBE), the Binge Eating Scale (BES), the Beck Depression Inventory (BDI), and body weight evaluation. Of the 6 patients who completed the trial, all showed reduced binge eating. Four patients presented a total remission, and 2 had a marked reduction in binge eating frequency. The mean DBE decreased significantly from 4.3 to 1.1 (P = 0.03), as did the BES scores, which fell from 31.8 to 15.3 (P = 0.04). Moreover, there was a statistically significant weight loss (mean 4.1 kg, P = 0.04). The most frequent side effects were paresthesias, fatigue, and somnolence. Topiramate may be an effective and well-tolerated agent in the treatment of BED in obese patients.


Effect of neoadjuvant treatment with anastrozole on tumour histology in postmenopausal women with large operable breast cancer.
Anastrozole is an orally active, non-steroidal aromatase inhibitor which appears effective as neoadjuvant treatment of breast cancer. Histological changes have been evaluated in biopsies from large, oestrogen-receptor rich, operable breast tumours in postmenopausal women following 12 weeks of neoadjuvant anastrozole treatment (1 mg (n=12) or 10 mg (n=11)). Of the 23 patients, 18 had a clinical response following treatment. Compared with pre-treatment biopsies anastrozole-treated specimens displayed decreased cellularity and/or increased fibrosis in 15 tumours; changes in gland formation, nuclear pleomorphism, or mitoses, in 12 cases; and a reduction in Mib1 score in all tumours. Marked changes in apoptotic scores were seen following treatment but the direction of effect was inconsistent. In all 17 tumours which were positive for progesterone receptors before therapy, treatment was associated with reduced staining for progesterone receptors. There was no consistent effect of treatment on oestrogen-receptor expression. It is concluded that neoadjuvant anastrozole treatment in this patient group has marked effects on tumour histopathology but these do not always correlate with clinical response.


Reductive dissolution and biomineralization of iron hydroxide under dynamic flow conditions.
Iron cycling and the associated changes in solid phase have dramatic implications for trace element mobility and bioavailability. Here we explore the formation of secondary iron phases during microbially mediated reductive dissolution of ferrihydrite-coated sand under dynamic flow conditions. An initial period (10 d) of rapid reduction, indicated by consumption of lactate and production of acetate and Fe-(II) to the pore water in association with a darkening of the column material, is followed by much lower rate of reduction to the termination of the experiment after 48 d. Although some Fe (<25%) is lost to the effluent pore water, the majority remains within the column as ferrihydrite (20-70%) and the secondary mineral phases magnetite (0-70%) and goethite (0-25%). Ferrihydrite converts to goethite in the influent end of the column where dissolved Fe(II) concentrations are low and converts to magnetite toward the effluent end where Fe(III) concentrations are elevated. A decline in the rate of Fe(II) production occurs concurrent with the formation of goethite and magnetite; at the termination of the experiment, the rate of reduction is <5% the initial rate. Despite the dramatic decrease in the rate of reduction, greater than 80% of the residual Fe remains in the ferric state. These results highlight the importance of coupled flow and water chemistry in controlling the rate and solid-phase products of iron (hydr)oxide reduction.


Understanding adsorption phenomena: investigation of the dye-cellulose interaction.
To understand the structural factors that control the adsorption of acid dyes onto cotton (cellulose), the adsorption of 15 acid dyes from water has been studied. An equilibrium exists between dye adsorbed in the cotton and dye in solution, and by measurement of the temperature dependence (277-333K) of the equilibrium constant, the enthalpy and entropy of binding are obtained. For most dyes adsorption is driven by the binding enthalpy, which is ascribed to van der Waals forces. Acid dyes consist of an aromatic core with peripheral solubilizing groups (generally sulfonates). Dyes in which the sulfonates are on one side of the molecule have the largest binding enthalpy. Assuming a binding geometry where the sulfonates protrude into water pools in the bulk amorphous regions and as much as possible of the dye core touches the surface, then a good correlation exists between the binding enthalpy and the summation of 1/r(6) over all the C, N, and O dye atoms, where r is the distance of each atom from the cellulose surface.


Rehabilitation of patients with venous diseases of the lower limbs: State of the art.
To date, no document comprehensively focused on the complex issue of the rehabilitation of chronic venous diseases of the lower limbs. This article overviews and summarizes current strategies concerning venous rehabilitation of lower limbs. Venous rehabilitation is based on four main strategies: (1) lifestyle adaptations and occupational therapies; (2) physical therapies; (3) adapted physical activities; (4) psychological and social support. Rehabilitative protocols must be tailored to the specific needs of each patient, depending on the severity of chronic venous disease and on the location and pattern of venous lesion(s), but also on age, motor deficits, co-morbidities and psychosocial conditions. Venous rehabilitation consists of non-pharmacologic and non-surgical interventions aiming at prevention of venous disease progression and complications, reduction of symptoms and improvement of quality of life. Well-designed clinical trials are required to evaluate the efficacy of the described rehabilitative protocols in influencing the evolution of venous disorders.


Predictors of smoking cessation in patients admitted for acute coronary heart disease.
Smoking cessation is probably the most important single action after a coronary event. In order to increase the effectiveness of smoking cessation programs, it is important to have knowledge of the predictors of smoking cessation. Further, it is unknown whether smoking cessation programs have impact on these predictors. Data were obtained from a randomized controlled trial of smoking cessation intervention in 240 smokers aged less than 76 years admitted for myocardial infarction, unstable angina, or cardiac bypass surgery. Baseline characteristics were prospectively recorded. Smoking cessation was determined by self report and biochemical verification at 12 months follow-up. In multivariate logistic regression analysis, a high level of nicotine addiction, low level of self-confidence in quitting and having previous coronary heart disease were significant negative predictors of smoking cessation at 12 months follow-up. Having previous coronary heart disease and a diagnosis other than acute myocardial infarction as a reason for admission were important negative predictors of abstinence in the usual care group, in contrast to the intervention group, although this did not reach a level of significance in the subgroup interaction analyses. A high level of nicotine addiction was a strong negative predictor in both groups. A high level of nicotine addiction is an important negative predictor of smoking cessation, even within an individualized smoking cessation program. Smoking cessation intervention seems to be especially effective in patients with previous coronary heart disease and in patients with unstable angina or coronary artery bypass surgery, compared to usual care.